Absence of the Arg441His polymorphism in the tryptophan hydroxylase 2 gene in adults with anxiety disorders and depression.
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Adult↗
Biomedical subjects
Deborah Gustafson
Publications and source records attributed to Deborah Gustafson.
Midlife respiratory function related to white matter lesions and lacunar infarcts in late life: the Prospective Population Study of Women in Gothenburg, Sweden.
BACKGROUND AND PURPOSE: Increased evidence suggests that poor respiratory function increases risk of ischemic damage to the brain. Longitudinal studies on respiratory function and cerebral small-vessel disease are lacking. We examined midlife and late-life respiratory function in relation to small-vessel disease on computed tomography (CT) in women followed for 26 years. METHODS: White matter lesions (WMLs) and lacunar infarcts were rated on brain CT scans in 2000 in 379 women 70 to 92 years of age from a longitudinal population study in Göteborg, Sweden. Respiratory function was measured by peak expiratory flow (PEF) in 1974 and 2000 and by forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) in 1980 and 2000. RESULTS: Lower FVC and FEV1 in 1980 and 2000 were associated with presence and severity of WMLs and lacunar infarcts in 2000. Per 1-SD decrease of FVC in 1980, odds ratios (95% CIs) were 1.49 (1.11 to 2.02) for presence of WMLs and 1.95 (1.34 to 2.84) for lacunar infarcts after adjustment for potential confounders. Per 1-SD decrease of FEV1 in 1980, adjusted odds ratios were 1.46 (1.06 to 2.00) for presence of WMLs and 1.42 (1.02 to 1.97) for lacunar infarcts. PEF in 1974 and 2000 was not associated with WMLs or lacunar infarcts. CONCLUSIONS: WMLs and lacunar infarcts in elderly women were related to lower midlife respiratory function. Although our data may not establish causation between lower respiratory function and small-vessel disease, they imply the importance of good respiratory function in midlife.
Brain↗
Midlife respiratory function and Incidence of Alzheimer's disease: a 29-year longitudinal study in women.
Normal cognitive function depends on sufficient supply and efficient utilization of oxygen in the brain. Prospective studies on respiratory function and dementia are lacking. This study investigated the relationship between midlife respiratory function and incidence of dementia in a population-based sample of 1291 women followed from 1974 to 2003. Respiratory function was measured by peak expiratory flow in 1974, and forced vital capacity and forced expiratory volume in 1980. Dementia diagnoses were based on information from neuropsychiatric examinations, informant interviews, hospital records and registry data. Better respiratory function in midlife was associated with a lower late-life risk of developing dementia and Alzheimer's disease (AD). Per 1 standard deviation increase in peak expiratory flow, forced vital capacity and forced expiratory volume, hazard ratios (95% confidence intervals) for dementia were 0.77 (0.65-0.91), 0.72 (0.57-0.92) and 0.75 (0.59-0.95), respectively, and for AD 0.76 (0.62-0.94), 0.71 (0.54-0.95) and 0.74 (0.56-0.98), respectively, after adjustment for potential confounders. These data reinforce the advantages of maintaining good respiratory function in midlife, even though causation cannot be established.
Aged↗
Skövde cataract study: I. Prevalence of lens opacities in a Swedish community.
OBJECTIVE: To study the prevalence of lens opacities in a well-defined Swedish population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Seven hundred inhabitants of the town of Skövde, Sweden were randomly selected and invited to an ophthalmologic examination. Invited persons were 70 to 84 years old and were assigned to 1 of 3 age groups: 70 to 74, 75 to 79, or 80 to 84. METHODS: All participants underwent visual acuity (VA) testing using the Early Treatment Diabetic Retinopathy Study acuity chart. Lens opacities were graded using the Lens Opacities Classification System III after pupil dilation. Causes of visual impairment, other than cataract, were identified by thorough ophthalmologic examination. MAIN OUTCOME MEASURE: Prevalence of lens opacities. RESULTS: Five hundred sixty-five persons underwent a complete examination (participation rate, 80.7%). As expected, the presence of lens opacities increased with age. Using a definition of cataract based on morphologic changes only, prevalences of cataract in one or both eyes were 23.5% for women and 14.0% for men in the entire cohort. If prevalence of previous cataract surgery was included, prevalence rose to 47.9% for women and 27.3% for men. In all age groups, lens opacities were denser and cataract prevalence was higher in women than in men. Consequently, VA was lower in females than in men, when other reasons for visual impairment were excluded. CONCLUSIONS: Lens opacities were common in the studied age groups and increased with age. In all studied age groups, lens opacities were denser in women than in men.
Age Distribution↗
Adiposity indices and dementia.
Indicators of adiposity, such as body-mass index (BMI), may be markers for changes in energy metabolism that influence dementia risk, progression, and ultimately death. Cross-sectional studies show that people with dementia have a lower BMI than those without dementia, which is potentially due to a greater rate of BMI decline occurring during the years immediately preceding dementia onset. However, a high BMI can also increase the risk for dementia when measured before clinical dementia onset, which might be due to vascular disorders or bioactive hormonal compounds that are secreted by adipose tissue. In this personal view, I consider how dementia is associated with BMI by looking at the role of BMI and obesity syndromes, mechanisms associated with adiposity, and the potential for hypothalamic dysregulation during the life course. Understanding the life course of adiposity by use of common surrogate measures, such as BMI, among those who do and do not develop dementia is relevant for understanding the causes of dementia and for shaping possible treatment options.
Adiposity↗
Update on hypertension and Alzheimer's disease.
Several studies report that blood pressure is increased in victims of Alzheimer's disease (AD) decades before the onset of the disease. Years before onset of Alzheimer's disease, blood pressure start to decrease and continues to decrease during the disease process. High blood pressure has also been related to pathological manifestations of Alzheimer's disease (senile plaques, neurofibrillary tangles, hippocampal atrophy). The exact mechanism behind these associations is not clear. Hypertension is also a risk factor for stroke, ischemic white matter lesions, silent infarcts, general atherosclerosis, myocardial infarction and cardiovascular diseases, and often clusters with other vascular risk factors, including diabetes mellitus, obesity and hypercholesterolemia. Also these risk factors have been related to Alzheimer's disease. Hypertension may thus cause cerebrovascular disease that may increase the possibility for individuals with AD encephalopathy to express a dementia syndrome. Hypertension may also lead to vessel wall changes in the brain, leading to hypoperfusion, ischemia and hypoxia which may initiate the pathological process of AD. Finally, subclinical AD may lead to increased blood pressure, and similar biological mechanisms may be involved in the pathogenesis of both disorders. Hypertension is a common disorder and often untreated. Several observational studies have reported that use of antihypertensives decreases risk of AD. Even though hypertension only results in a moderately increased risk of AD, or overall dementia, better treatment of hypertension may have an immense effect on the total number of demented individuals.
Alzheimer Disease↗
Cholesterol and Alzheimer's disease--is there a relation?
The predominating theory on the pathophysiology of Alzheimer's disease (AD) concerns the mis-metabolism of amyloid precursor protein (APP). As a result of this mis-metabolism, there is an increased production of the 42 amino acid form of beta-amyloid (Abeta42) that rapidly will form oligomers that initiates a cascade of events leading to the accumulation of amyloid plaques. Commonly recognised as vascular factors, hypertension, hypercholesterolemia and diabetes and the inheritance of the epsilon4 allele of the APOE gene, are also risk factors for AD. These risks have been found to promote the production of Abeta42. An association between cholesterol and the development of AD was suggested in the early 1990s and ever since, an increasing amount of research has confirmed that there is a link between cholesterol and the development of AD. A high cholesterol levels in mid-life is a risk for AD and statins, i.e., cholesterol-lowering drugs, reduce this risk. Statins may not only inhibit enzymes involved in the endogenous synthesis of cholesterol but also affect enzymes involved in Abeta metabolism, i.e., alpha-secretase and beta-secretase. This normalises the breakdown of APP thereby promoting the non-amyloidogenic pathway. In this review, investigations focusing on cholesterol and Alzheimer's disease are presented.
Alzheimer Disease↗
Body mass index, other cardiovascular risk factors, and hospitalization for dementia.
BACKGROUND: Previous studies have shown that risk factors commonly associated with coronary disease, stroke, and other vascular disorders also predict dementia. We investigated the longitudinal relationship between body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) and risk of hospital discharge or death certificate diagnosis of dementia. METHODS: A total of 7402 men who were 47 to 55 years old in 1970 to 1973, without prior stroke or myocardial infarction, derived from a population sample of 9998 men were prospectively followed up until 1998. Two hundred fifty-four men (3.4%) had a hospital discharge diagnosis or a death certificate diagnosis of dementia: 176 with a primary diagnosis or cause of death and 78 with a secondary diagnosis. RESULTS: The relationship between BMI and dementia as a primary diagnosis was J-shaped, and men with a BMI between 20.00 and 22.49 had the lowest risk. Subsequently, after adjustment for smoking, blood pressure, serum cholesterol level, diabetes mellitus, and social class, the risk increased linearly in men who had a BMI of 22.50 to 24.99 (multiple-adjusted hazard ratio [HR], 1.73; 95% confidence interval [CI], 0.92-3.25), 25.00 to 27.49 (HR, 1.93; 95% CI, 1.03-3.63), 27.50 to 29.99 (HR, 2.30; 95% CI, 1.18-4.47), and 30.00 or greater (HR, 2.54; 95% CI, 1.20-5.36) (P for linear trend = .03). Men with a BMI less than 20.00 had a nonsignificantly elevated risk (HR, 2.19; 95% CI, 0.77-6.25). CONCLUSIONS: A J-shaped relationship was observed between BMI and dementia, such that a BMI less than 20 and an increasing BMI of 22.5 or greater were associated with increased risk from midlife to old age of a primary hospital diagnosis of dementia. Overweight and obesity could be major preventable factors in the development of dementia.
Body Mass Index↗
Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.
BACKGROUND: Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD). OBJECTIVE: To examine the relationship between antioxidant supplement use and risk of AD. DESIGN: Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. Supplement use was ascertained at the first contact. SETTING: Cache County, Utah. PARTICIPANTS: Among 4740 respondents (93%) with data sufficient to determine cognitive status at the initial assessment, we identified 200 prevalent cases of AD. Among 3227 survivors at risk, we identified 104 incident AD cases at follow-up. MAIN OUTCOME MEASURE: Diagnosis of AD by means of multistage assessment procedures. RESULTS: Analyses of prevalent and incident AD yielded similar results. Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B-complex supplements. CONCLUSIONS: Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD.
Aged↗
Development of a food frequency questionnaire to estimate calcium intake of Asian, Hispanic, and white youth.
OBJECTIVE: To develop a food frequency questionnaire (FFQ) that estimates calcium intake of Asian, Hispanic, and white youth living in the western United States. DESIGN: A list of 80 foods was assembled to create an FFQ to measure calcium intake. Evaluation of the FFQ spanned four consecutive weeks. An FFQ was completed during Week 1 and Week 4, and a 24-hour dietary recall was completed during Week 2 and Week 3.Subjects/setting A convenience sample of 162 Asian, Hispanic, and white youth ages 10 to 18 years was selected. Statistical analyses performed Percent agreement, paired t tests, Pearson correlation coefficients of cube-root transformed values, and deattenuated Pearson correlation coefficients of cube-root transformed values were used to evaluate the FFQ. RESULTS: The correlation between calcium intake estimates, when measured by first and second administrations of the FFQ, was 0.68 (Pearson's r) for the total sample. Correlations differed by age, sex, and ethnic subgroups as follows: 10 to 13 years (r=0.62), 14 to 18 years (r=0.73), male (r=0.73), female (r=0.64), Asian (r=0.77), Hispanic (r=0.72), and white (r=0.48). The correlation between calcium intakes as estimated by the second FFQ vs the average of the two 24-hour dietary recalls was 0.54 (deattenuated Pearson's r) for the total sample. This correlation differed by age, sex, and ethnic subgroups as follows: 10 to 13 years (r=0.46), 14 to 18 years (r=0.59), male (r=0.65), female (r=0.45), Asian (r=0.64), Hispanic (r=0.18), and white (r=0.57). CONCLUSIONS: A unique dietary survey has been developed to estimate calcium intake among Asian, Hispanic, and white youth in the United States.
Adolescent↗
Evolutionary rather than revolutionary progress in dementia.
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Animals↗
An 18-year follow-up of overweight and risk of Alzheimer disease.
BACKGROUND: Overweight and obesity are epidemic in Western societies and constitute a major public health problem because of adverse effects on vascular health. Vascular factors may play a role in the development of a rapidly growing disease of late life, Alzheimer disease (AD). Using body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters), we examined whether overweight is a risk factor for dementia and AD. METHODS: The relationship between BMI and dementia risk was investigated in a representative cohort of 392 nondemented Swedish adults who were followed up from age 70 to 88 years, with the use of neuropsychiatric, anthropometric, and other measurements. Multivariate Cox proportional hazards regression analyses included BMI, blood pressure, cardiovascular disease, cigarette smoking, socioeconomic status, and treatment for hypertension. RESULTS: During the 18-year follow-up (4184.8 risk-years), 93 participants were diagnosed as having dementia. Women who developed dementia between ages 79 and 88 years were overweight, with a higher average BMI at age 70 years (27.7 vs 25.7; P =.007), 75 years (27.9 vs 25.0; P<.001), and 79 years (26.9 vs 25.1; P =.02) compared with nondemented women. A higher degree of overweight was observed in women who developed AD at 70 years (29.3; P =.009), 75 years (29.6; P<.001), and 79 years (28.2; P =.003) compared with nondemented women. For every 1.0 increase in BMI at age 70 years, AD risk increased by 36%. These associations were not found in men. CONCLUSIONS: Overweight is epidemic in Western societies. Our data suggest that overweight at high ages is a risk factor for dementia, particularly AD, in women. This may have profound implications for dementia prevention.
Aged↗
Calcium intake of Asian, Hispanic and white youth.
OBJECTIVE: To examine calcium intake and food sources among Asian, white and Hispanic youth, in order to develop and target interventions to improve calcium intake. METHODS: Cross-sectional survey with two 24-hour dietary recalls one week apart. Calcium intake was evaluated in 167 male and female adolescents of Asian, Hispanic and white ethnicity, ages 10-18 years, from six states. Main outcome measures were mean daily calcium intake (mg/day). STATISTICAL ANALYSES PERFORMED: t tests, Chi-square and analysis of variance for differences by age, ethnicity and gender, multiple regression of factors influencing calcium intake. RESULTS: Overall median calcium intake was 938 mg/day with 868 mg/day for Asians, 1180 mg/day for whites and 896 mg/day for Hispanics. Daily milk intake was the primary predictor of calcium intake with Asian ethnicity and female gender each showing a negative association to calcium intake in multiple regression models. CONCLUSIONS: Milk intake was the primary factor positively influencing calcium intake, while Asian ethnicity and female gender negatively influenced calcium intake. Thus, interventions to improve calcium intake should focus on improving milk intake of Asians and females.
Adolescent↗
Hypertension, hypertension-clustering factors and Alzheimer's disease.
Hypertension is a risk factor for stroke, ischemic white matter lesions, silent infarcts, general atherosclerosis, myocardial infarction and cardiovascular morbidity and mortality. This risk increases with increasing blood pressure also at blood pressure within the normal ranges, and a high percentage of these cardiovascular events occur in those with normal blood or mild hypertension. Several studies have reported that high blood pressure precedes Alzheimer's disease by decades, but blood pressure decreases the years before dementia onset and is lower in individuals with Alzheimer's disease than in controls. High blood pressure has also been related to the neuropathological manifestations of Alzheimer's disease. Hypertension often clusters with other vascular risk factors, including diabetes mellitus, obesity, and hypercholesterolemia. Also, these risk factors have been related to Alzheimer's disease. The exact mechanism behind these associations is not clear. Hypertension may cause cerebrovascular disease that may increase the likelihood that individuals with AD encephalopathy will express a dementia syndrome, but hypertension may also accelerate the AD process, subclinical AD may lead to increased blood pressure, and similar biological mechanisms may be involved in the pathogenesis of both disorders. Hypertension is a common disorder and often untreated. Even if hypertension only results in a moderately increased risk of AD, or overall dementia, better treatment of hypertension may have an immense effect on the total numbr of demented individuals.
Alzheimer Disease↗
Hypertension and related factors in the etiology of Alzheimer's disease.
The prevalence of hypertension is estimated to approach 50% in individuals above age 70. The consequences of hypertension include cerebrovascular disease, coronary heart disease, and general atherosclerosis. Several recent studies suggest that there may be an association also between hypertension and Alzheimer's disease (AD). This review will examine the evidence for this association and possible pathways between hypertension, Alzheimer encephalopathy, and clinical dementia.
Aged↗
Perspectives on intake of calcium-rich foods among Asian, Hispanic, and white preadolescent and adolescent females.
OBJECTIVE: Declining calcium intake among adolescents warrants attention. Our objective was to identify influences on adolescents' consumption of calcium-rich foods. DESIGN: Focus groups were conducted with girls representing 2 age groups (11 to 12 or 16 to 17 years) and 3 macroethnic groups (Asian, Hispanic, or white). SETTING: Public schools in 10 states. PARTICIPANTS: A convenience sample (n = 200) was recruited through schools. VARIABLES MEASURED: Focus groups (n = 35) were audiotaped and transcribed. Influences relative to consumption of milk or other calcium-rich foods were identified. ANALYSIS: Comments were coded as motivators or barriers within each focus group. Content analysis procedures were used to compare ethnic and age groups. RESULTS: A barrier to milk consumption that was more common among older girls and Asian groups was the limited expectation within families for drinking milk. Many controlled their own beverage choices, and milk, even if liked, was only one option. Milk was positively associated with strength and bone health, but these attributes were viewed as being more important for boys than girls. Milk was associated with breakfast, school lunches, cereal, and desserts. White girls had the most positive reactions to milk and Hispanic girls the most negative. All groups were positive toward pizza, ice cream, and cheese. CONCLUSIONS AND IMPLICATIONS: To improve calcium intake among teens, interventions should include a family component, stress the benefits of milk for girls, and focus on breakfast.
Adolescent↗
Low serum potassium in mid life associated with decreased cerebrospinal fluid Abeta42 in late life.
Low serum potassium increases risk of hypertension and stroke, and cardiovascular factors increase the risk of Alzheimer disease (AD). We examined the association between serum potassium and the biologic marker cerebrospinal fluid amyloid-beta (Abeta42), which is decreased in Alzheimer disease patients. Psychiatric examinations, laboratory and other tests were conducted on a population-based sample of 1080 women aged 46 to 60 in 1968, with follow-ups in 1974, 1980, and 1992. In 1992, cerebrospinal fluid Abeta42 levels were obtained from 81 women. Increasing serum potassium in 1968 was associated with increasing cerebrospinal fluid Abeta42 (beta = 153.9, P = 0.041) in 1992 using age-adjusted linear regression. Compared with the lowest tertile of potassium, the middle (beta = 95.3, P = 0.138) and highest tertiles (beta = 193.5, P = 0.004) had incrementally increased cerebrospinal fluid Abeta42 levels. Associations remained after controlling for blood pressure and other factors, and were similar among the 17 women in 1974 with available serum potassium. Potassium in 1980 and 1992 was not associated with cerebrospinal fluid Abeta42. Findings suggest low serum potassium in mid life, but not late life, is associated with low cerebrospinal fluid Abeta42 levels in late life. It is possible potassium co-varies with another variable that is associated with cerebrospinal fluid Abeta42. Nonetheless, serum potassium is a modifiable risk factor and further examination of the potassium-dementia relationship is warranted.
Adult↗